Effects of Bilateral Jugular Vein Ligation on Local Cerebral Blood Flow

The authors examined the effect of bilateral jugular vein ligation (JVL) on local cerebral blood flow (CBF). Local CBF was measured in the neocortex of the frontal lobe over a 1-week period in 10 freely moving male rats. Measurements were taken with the hydrogen clearance method before and after the rat underwent either an operation of bilateral JVL or a sham operation. After the sham operation, blood flow values did not change significantly compared with preoperative values. Blood flow values decreased rapidly in rats with JVL. For 3 hours after surgery, JVL values were significantly lower (p <0.05) than preoperative values were, then gradually they recovered and reached preoperative values within 48 hours. Histopathologic study showed no remarkable parenchymal damages in the brain of rats with JVL. These results show that bilateral JVL produces a reversible decrease in the CBF and does not cause histopathologic brain damages.     

Effect of experimental common carotid arteriotomy on cerebral blood flow in rats

Cerebral blood flow (CBF) and its reactivity to alterations in arterial carbon dioxide tension were measured in 52 rats. Measurements were made in four groups of rats: 15 were controls, 14 had one carotid artery clamped, 11 had microvascular common carotid arteriotomies, and 12 had sham arteriotomies. Before carotid operation, a flow change of 1 ml/100 g of brain per minute per torr change in CO2 tension was demonstrated in the rats, a value for reactivity similar to that found in normal humans. After unilateral common carotid ligation, CBF was not significantly disturbed in either hemisphere, and reactivity was preserved. In rats subjected to arteriotomy, CBF fell by 30% from the control level in both hemispheres, and carbon dioxide reactivity was reduced by 80%. Very similar reductions in flow (38%) and reactivity (76%) were produced after sham arteriotomy, in which the common carotid artery was isolated between temporary clamps for 30 minutes, but the arteriotomy incision was not made. The observed flow reduction and carbon dioxide reactivity impairment must result from the reperfusion of the brain through the traumatized carotid artery, inasmuch as no impairment of either flow or reactivity followed extravascular dissection and permanent ligation of the vessel. These changes may be mediated by damage to the sympathetic plexus or the innervation of the carotid body chemoreceptors or by the release of histamine, prostaglandins, or other vasoactive substances from the incised vessel wall. If this finding is applicable to humans, it suggests that the entire cerebral circulation in patients with respiratory impairment may be precarious for some hours after a carotid endarterectomy and confirms the danger of hypercapnia during anesthesia for carotid surgery.     

Regional blood flow and cerebral metabolic changes during alcohol withdrawal and following midazolam therapy

Regional blood flows and cerebral oxygen consumption (CMRO2) were measured following alcohol withdrawal in alcohol-dependent rats. In addition, the authors tested the ability of midazolam (0.057, 0.575, or 5.75 mg X kg-1) to modify alcohol-induced changes. Rats received a 3-week treatment of daily ad libitum access to a liquid diet containing 6.54% ethanol or a sham treatment with the same caloric intake but with white dextrin substituted for alcohol. Regional blood flow was measured 12 h after alcohol withdrawal with radioactive microspheres. Nitrous oxide (70% in oxygen) was used as the control anesthetic. Rats withdrawn from alcohol treatment had significantly increased heart rate, cortical cerebral blood flow (CBF) (39 +/- 8%, mean +/- SE), and CMRO2 (41 +/- 9%) compared with sham-treated rats (P less than 0.05). Subcortical CBF (49 +/- 8%), myocardial (52 +/- 18%), and hepatic arterial blood flow (298 +/- 47%) also were increased in alcohol-withdrawn rats. Renal blood flow decreased 47 +/- 5%, while skeletal muscle and small intestinal blood flow were not significantly different between the two groups. Midazolam infusion decreased CBF, CMRO2, and hepatic arterial blood flow in alcohol-withdrawn rats to similar levels as sham-treated rats and increased renal blood flow in both groups. Skeletal muscle and intestinal tissues showed no change in blood flow in response to midazolam. The authors conclude that midazolam may be effective in lowering blood pressure and brain metabolism and reversing regional blood flow changes produced by alcohol withdrawal in the rat.     

Acute regional cerebral blood flow changes caused by severe head injuries

To evaluate the changes in cerebral blood flow (CBF) that occur immediately after head injury and the effects of different posttraumatic lesions on CBF, 61 CBF studies were obtained using the xenon-computerized tomography method in 32 severely head-injured adults (Glasgow Coma Scale score (GCS) less than or equal to 7). The measurements were made within 7 days after injury, 43% in the first 24 hours. During the 1st day, patients with an initial GCS score of 3 or 4 and no surgical mass had significantly lower flows than did those with a higher GCS score or mass lesions (p less than 0.05): in the first 1 to 4 hours, those without surgical mass lesions had a mean CBF of 27 cc/100 gm/min, which rose to 44 cc/100 gm/min by 24 hours. Patients without surgical mass lesions who died tended to have a lower global CBF than did those with better outcomes. Mass lesions were associated with a high global CBF and bihemispheric contusions with the lowest flows. By 24 hours after injury, global blood flow increased in groups that originally had low flows and decreased in those with very high initial flows, such that by 36 to 48 hours, most patients had CBF values between 32 and 55 cc/100 gm/min. Lobar, basal ganglion, and brain-stem blood flow values frequently differed by 25% or more from global averages. Brain-stem CBF varied the most but did not correlate with clinical signs of brain-stem dysfunction. Double studies were performed at two different pCO2 values in 10 patients with various posttraumatic lesions, and the CO2 vasoresponsivity was calculated. Abnormal CO2 vasoresponsivity was found with acute subdural hematomas and defuse cerebral swelling but not with epidural hematomas. In patients without surgical mass lesions, the findings suggest that CBF in the first few hours after injury is often low, followed by a hyperemic phase that peaks at 24 hours. Global CBF values vary widely depending on the type of traumatic brain injury, and brain-stem flow is often not accurately reflected by global CBF values. These findings underscore the need to define regional CBF abnormalities in victims of severe head injury if treatment is intended to prevent regional ischemia.     

Traumatic brain injury creates biphasic systemic hemodynamic and organ blood flow responses in rats

Traumatic brain injury affects systemic circulation as well as directly damages the brain. The present study examined the effects of fluid percussion brain injury on systemic hemodynamics and organ arterial blood flow in rats. Rats were prepared for fluid percussion injury under anesthesia. Twenty-four hours later, rats were anesthetized (1.0% halothane in N2O:O2) and prepared for radioactive microsphere measurement of cardiac output and organ blood flow. After baseline blood flow and physiological measurements were established, the rats were injured (2.47 +/- 0.02 atm, n = 17) or not injured (n = 20). Additional blood flow determinations were made at two of the following four time (T) points: 5, 15, 30, and 60 min after the injury or sham injury. Fluid percussion brain injury produced an immediate systemic hypertension followed by a hypotension and low cardiac output. Organ blood flows remained constant or increased for 30 min and then declined. Decreased blood flow was most pronounced in the kidneys and the spleen and was less severe in the liver. The reduced cardiac output was redistributed to favor blood flow through the heart and pancreas. These data suggest that traumatic brain injury creates a hyperdynamic period followed by a hypodynamic state with a heterogeneous hypoperfusion among organs.     

Periischemic cerebral blood flow (CBF) does not explain beneficial effects of isoflurane on outcome from near-complete forebrain ischemia in rats

BACKGROUND: Isoflurane improves outcome from near-complete forebrain ischemia in rats compared with fentanyl-nitrous oxide (N2O). Sympathetic ganglionic blockade with trimethaphan abolishes this beneficial effect. To evaluate whether anesthesia-related differences in cerebral blood flow (CBF) may explain these findings, this study compared regional CBF before, during, and after near-complete forebrain ischemia in rats anesthetized with either isoflurane (with and without trimethaphan) or fentanyl-nitrous oxide. METHODS: Fasted, normothermic isoflurane anesthetized Sprague-Dawley rats were prepared for near-complete forebrain ischemia (10 min of bilateral carotid occlusion and mean arterial pressure = 30 mmHg). After surgery, rats were anesthetized with either 1.4% isoflurane (with or without 2.5 mg of trimethaphan intravenously at onset of ischemia) or fentanyl-nitrous oxide (25 microgram. kg-1. h-1. 70% N2O-1). Regional CBF was determined (14C-iodoantipyrine autoradiography) before ischemia, 8 min after onset of ischemia, and 30 min after onset of reperfusion. RESULTS: Regional CBF did not differ significantly among groups at any measurement interval. Ischemia caused a marked flow reduction to 5% or less of baseline (P < 0.001) in selectively vulnerable regions, such as the cortex, caudoputamen and hippocampus, whereas flow in the brain stem and cerebellum was preserved. Reperfusion at 30 min was associated with partial restoration of flow to 35-50% of baseline values in ischemic structures. CONCLUSIONS: The results indicate that improved histologic-behavioral outcome provided by isoflurane anesthesia cannot be explained by differential vasodilative effects of the anesthetic states before, during, or after severe forebrain ischemia. This study also shows severe postischemic delayed hypoperfusion that was not affected by choice of anesthetic or the presence of trimethaphan. Mechanisms other than effects on periischemic CBF must be responsible for beneficial effects of isoflurane in this model.     

Cerebral pressure autoregulation is intact and is not influenced by hypothermia after traumatic brain injury in rats

In head-injured patients and experimental traumatic brain injury (TBI), important cerebrovascular abnormalities include decreases in cerebral blood flow (CBF) and impairment of cerebral pressure autoregulation. We evaluated CBF and pressure autoregulation after fluid percussion injury (FPI) and hypothermia in rats with the hypothesis that hypothermia would ameliorate changes in posttraumatic CBF. Male Sprague-Dawley rats, intubated and mechanically ventilated, were prepared for parasagittal FPI (1.8 atm) and laser Doppler CBF flow (LDF) measurement. The abdominal aorta was cannulated for rapid removal and reinfusion of blood. Baseline autoregulatory testing in all groups consisted of LDF measurements at normothermia and a mean arterial pressure (MAP) of 100 mm Hg, followed by randomly ordered changes of MAP to 80, 60, and 40 mm Hg. Animals were then randomized to one of five groups: normothermic control without FPI; normothermia with FPI; hypothermic control (32 degrees C) without FPI; hypothermia initiated before FPI; and hypothermia initiated immediately after FPI injury. For each group, a complete, randomly ordered autoregulatory sequence was performed at 30 and 60 min after FPI or sham TBI. In a second study, rats were prepared identically, maintained at normothermic temperatures and autoregulation was tested before and after TBI using a set of randomly ordered levels of hypotension or using progressive reductions in MAP (i.e., 80, 60, 40 mm Hg) with the hypothesis that the technical manner and timing of decreasing of the blood pressure would effect CBF after TBI. Due to high acute mortality, the group in which hypothermia was induced before FPI was excluded from the analysis. At baseline, autoregulation was similar in all groups. There was no change in CBF or autoregulation in the normothermic control group at 30 and 60 min. In the other groups at 30 and 60 min, there was a similar, statistically significant decrease in absolute CBF (i.e., a decrease of 27-57% of baseline values), but pressure autoregulation was intact except at the lowest blood pressure tested at 60 min, where there was a slight improvement in the hypothermic group. Thus, in these experiments, absolute CBF decreased with hypothermia and FPI, while neither hypothermia nor FPI significantly altered autoregulation. In the second study, autoregulatory function was not different before TBI when comparing random and sequential blood pressure changes, but, when comparing the groups after TBI at the 60 mm Hg blood pressure level, CBF was significantly lower in the sequential group than in the random order group. This suggests that the mechanism of creating hypotension, whether random or sequential, significantly affects the measurement of CBF and autoregulation after TBI in rats.     

Periischemic Cerebral Blood Flow (CBF) Does Not Explain Beneficial Effects of Isoflurane on Outcome from Near-complete Forebrain Ischemia in Rats

Background: Isoflurane improves outcome from near-complete forebrain ischemia in rats compared with fentanyl-nitrous oxide (N2O). Sympathetic ganglionic blockade with trimethaphan abolishes this beneficial effect. To evaluate whether anesthesia-related differences in cerebral blood flow (CBF) may explain these findings, this study compared regional CBF before, during, and after near-complete forebrain ischemia in rats anesthetized with either isoflurane (with and without trimethaphan) or fentanyl-nitrous oxide.

Methods: Fasted, normothermic isoflurane anesthetized Sprague-Dawley rats were prepared for near-complete forebrain ischemia (10 min of bilateral carotid occlusion and mean arterial pressure = 30 mmHg). After surgery, rats were anesthetized with either 1.4% isoflurane (with or without 2.5 mg of trimethaphan intravenously at onset of ischemia) or fentanyl-nitrous oxide (25[mu]g [middle dot] kg-1 [middle dot] h-1 [middle dot] 70% N2O-1). Regional CBF was determined (14C-iodoantipyrine autoradiography) before ischemia, 8 min after onset of ischemia, and 30 min after onset of reperfusion.

Results: Regional CBF did not differ significantly among groups at any measurement interval. Ischemia caused a marked flow reduction to 5% or less of baseline (P < 0.001) in selectively vulnerable regions, such as the cortex, caudoputamen and hippocampus, whereas flow in the brain stem and cerebellum was preserved. Reperfusion at 30 min was associated with partial restoration of flow to 35-50% of baseline values in ischemic structures.     

Cerebral blood flow at one year after controlled cortical impact in rats: assessment by magnetic resonance imaging

Progressive tissue loss and delayed cognitive deficits are seen in rats during the initial year after experimental traumatic brain injury (TBI). As much as 10% of parenchymal volume is lost even in the contralateral hemisphere by 1 year after controlled cortical impact (CCI) in rats. Progressive declines in cerebral blood flow (CBF) are also associated with advanced age and neurodegenerative diseases. Surprisingly, the long-term effects of TBI on CBF remain undefined. CBF was quantified by continuous arterial spin-labeled magnetic resonance imaging (MRI) and measurements of spin-lattice relaxation time in a slice through the plane of injury at 1 year after experimental TBI produced by CCI (n = 4) or sham surgery (n = 4) in rats. CBF was quantified in six regions of interest (ROIs) that were anatomically identified on the control images in each hemisphere and included a medial cortical segment (contusion-enriched, beneath the impact site, on the ipsilateral side) cortex, hippocampus, thalamus, amygdala/pyriform cortex, and hemisphere. At 1 year after injury, CBF was dramatically (96%) reduced in structures within the large cystic lesion that was seen in three of four rats and variably included cortex and hippocampus. Overall, there was an 80% reduction in CBF in the ipsilateral medial cortical segment comparing CCI and sham groups. Similarly, 52% and 67% reductions were seen in CBF in the cortical and hippocampal ROIs ipsilateral to impact (CCI vs. sham), respectively. These are regions both with marked CBF disturbances early after injury and that ultimately suffer considerable tissue loss over the 1-year interval. However, at 1 year after CCI, CBF was not different from sham in other ROIs, including ipsilateral thalamus, or either contralateral hippocampus or hemisphere. We conclude that, at 1 year after CCI, CBF is reduced in anatomic structures at or near the impact site, including injured cortex and hippocampus, and this translates into a reduction in hemispheric CBF. However, despite both significant occult tissue loss ipsilateral and contralateral to the injury and delayed cognitive deficits, widespread reductions in CBF are not observed. This suggests the possibility of remodeling or repackaging of the brain that preserves CBF outside of the cystic lesion.     

Correlation of the extracellular glutamate concentration with extent of blood flow reduction after subdural hematoma in the rat.

The excitatory neurotransmitters glutamate and aspartate are an important factor in the causation of ischemic brain damage. The concentration of glutamate and aspartate was serially measured in extracellular fluid using in vivo microdialysis after induction of a subdural hematoma or after a sham operation in the rat. Measurements were made in the cortex underlying the hematoma and in the ipsilateral hippocampus, and these findings were correlated with regional cerebral blood flow (CBF), measured autoradiographically 2 hours after hematoma induction. In the severely ischemic cortex underlying the hematoma (mean CBF less than 25 ml/100 gm/min), glutamate and aspartate content increased more than 750% over basal levels. In individual animals the magnitude of glutamate release correlated with the extent of the focal ischemic zone under the hematoma (r = 0.907). Hippocampal glutamate levels rose 339%, yet regional CBF was preserved (114 ml/100 gm/min). This accords with focal hypermetabolism in this model, and may imply a glutamate-mediated "excitotoxic" process after subdural hematoma.     

Cerebral circulation and metabolism after severe traumatic brain injury: the elusive role of ischemia

Although experimental and pathological studies suggest an important role for ischemia in the majority of fatal cases of traumatic brain injury, ischemia has been a rare finding in most clinical studies of cerebral blood flow (CBF) in head-injured patients. The hypothesis of the present study was that cerebral ischemia occurs in the first few hours after injury, but that CBF measurements have not been performed early enough. Early measurements of CBF (by the 133Xe intravenous method) and arteriovenous oxygen difference (AVDO2) were obtained in 186 adult head-injured patients with a Glasgow Coma Scale score of 8 or less, and were correlated with neurological status and outcome. During the first 6 hours after injury, CBF was low (22.5 +/- 5.2 ml/100 gm/min) but increased significantly during the first 24 hours. The AVDO2 followed the opposite course; the decline of AVDO2 was most profound in patients with low motor scores, suggesting relative hyperemia after 24 hours. A significant correlation between motor score and CBF was found in the first 8 hours after injury (Spearman coefficient = 0.69, p less than 0.001), but as early as 12 hours postinjury this correlation was lost. A similar pattern was found for the relationship between CBF and outcome. Cerebral blood flow below the threshold for infarction (CBF less than or equal to 18 ml/100 gm/min) was found in one-third of the studies obtained within 6 hours, the incidence rapidly decreasing thereafter. A low CBF after 24 hours was not generally associated with a high AVDO2, and was probably a reflection of low oxidative metabolism rather than frank ischemia. In 24 patients, a CBF of 18 ml/100 gm/min or less was found at some point after injury; the mortality rate was significantly higher in this subgroup, and survivors did worse. In some cases, ischemia was successfully treated by reducing hyperventilation or inducing arterial hypertension. These results support the above hypothesis, and suggest that early ischemia after traumatic brain injury may be an important factor determining neurological outcome. Moreover, these data indicate that early hyperventilation or lowering of blood pressure to prevent brain edema may be harmful.     

Pitfalls of Commonly Used Ischemic and Dementia Models Due to Early Seizure by Carotid Ligation

While the bilateral common carotid artery (CCA) ligation model is widely used in cerebrovascular disease and dementia studies, it can frequently cause seizures. We examined the validity of seizure as an experimental model of ischemia. Eight-week-old male Wistar and Sprague-Dawley (SD) rats were implanted with electrocorticography (ECoG) electrodes and bilateral CCA ligation was performed and compared to the sham groups. ECoG monitoring was used to confirm the seizure discharge and count the number of spikes in the interictal phase 2 h after ligation, followed by power spectral analysis. Magnetic resonance imaging (MRI) was performed 6 h after bilateral CCA ligation to assess fractional anisotropy (FA), apparent diffusion coefficient (ADC), and cerebral blood flow (CBF) values. Magnetic resonance spectroscopy (MRS) was also performed and the ischemic parameters and electrophysiological changes were compared. The Wistar rat group had significantly higher mortality, frequency of seizures, incidence of non-convulsive seizures, and number of spikes in the interictal period compared to those in the SD rat group. Power spectral analysis showed increased power in the delta band in both Wistar and SD rat groups. MRI, after CCA ligation, showed significantly lower ADC values, lower glutamine and glutamate levels, and higher lactate values in Wistar rats, although there was no difference in FA values. Metabolic and electrophysiological changes after CCA ligation differed according to the rat strain. Wistar rats were prone to increased lactate and decreased glutamine and glutamate levels and the development of status epilepticus. Seizures can affect the results of ischemic experiments.     

A new rat model of diffuse brain injury associated with acute subdural hematoma: assessment of varying hematoma volume,insult severity,and the presence of hypoxemia

The aim of this study was to develop a new rat model of diffuse brain injury (DBI) associated with acute subdural hemorrhage (SDH). In order to make this model more clinically relevant, we determined whether the varying hematoma volume, severity of DBI, or the presence of hypoxemia could influence the physiological consequence. SDH was made by an autologous blood injection, while DBI was induced using the impact acceleration model (mild, 450 g/1 m, severe, 450 g/2 m). Physiological parameters measured included intracranial pressure (ICP), mean arterial blood pressure (MABP), cerebral blood flow (CBF), and brain tissue water content. In the first series, 23 rats were randomized into the five following groups: Group 1, sham; Group 2, 400 (microL SDH; Group 3, SDH400 + mild DBI; Group 4, SDH400 + severe DBI; and Group 5, SDH300 + severe DBI. Results suggested that SDH300 + severe DBI (Group 5) may be the most suitable model, in which the MABP and CBF temporarily decreased during the SDH induction, but thereafter recovered to the baseline. Conversely, ICP was persistently elevated throughout the experiment. The water content was also significantly higher in both hemispheres compared to that of sham. In the second series, the animal was exposed to a hypoxemic insult (10 or 30 min) in addition to SDH300 + severe DBI (Group 6). The prolonged hypoxemia caused both a severe CBF reduction without recovery and a bilateral brain swelling, whereas the brief hypoxemia showed a gradual CBF recovery from the transient reduction and an increased water content only in the SDH side. These results suggest that these models may be potentially useful to study the combination of DBI and SDH with or without hypoxemia.     

Changes in cerebral energy metabolites induced by impact-acceleration brain trauma and hypoxic-hypotensive injury in rats

The aim of this study was to describe, in rats, brain energy metabolites changes after different levels of head trauma (T) complicated by hypoxia-hypotension (HH). Male Sprague Dawley rats (n = 7 per groups) were subjected to T by impact-acceleration with 450-g weight drop from 1.50 or 1.80 m (T 1.50 or T 1.80), or to a 15-min period of HH (controlled hemorrhage to mean arterial pressure [MAP] of 40 mm Hg, and mechanical ventilation with N(2) 90%/O(2) 10%), or to their association (T followed by HH). Invasive MAP, intraparenchymental intracranial pressure (ICP), and cerebral blood flow (CBF using Laser Doppler flowmetry) were recorded during the 5 post-traumatic hours. Cerebral microdialysis was used to measure each hour interstitial brain glucose, lactate, pyruvate, and glutamate. For the entire period, the levels of cerebral glucose, pyruvate, and glutamate were not statistically different between groups. In addition, there were no differences associated with the lactate-glucose ratio. Lactate was significantly higher overtime only in T 1.80 + HH group (p < 0.001 vs. every other groups). The lactate-pyruvate ratio increased with trauma level, and was significantly different vs. sham for the entire study period in T 1.50 + HH, in T 1.80, and in T 1.80 + HH. There was no correlation between CBF variations and the lactate-pyruvate ratio (r(2) = 0.00001). The cerebral perfusion pressure was greater than 70 mm Hg in all groups. The prolonged post-traumatic impairment in brain energy metabolism may be related to traumatic brain injury (TBI) severity. It became worse when T was complicated by HH, but was not related to changes in CBF.     

Effects of hyperbaric oxygenation

OBJECT: Hyperbaric oxygenation (HBO) therapy has been shown to reduce mortality by 50% in a prospective randomized trial of severely brain injured patients conducted at the authors' institution. The purpose of the present study was to determine the effects of HBO on cerebral blood flow (CBF), cerebral metabolism, and intracranial pressure (ICP), and to determine the optimal HBO treatment paradigm. METHODS: Oxygen (100% O2, 1.5 atm absolute) was delivered to 37 patients in a hyperbaric chamber for 60 minutes every 24 hours (maximum of seven treatments/patient). Cerebral blood flow, arteriovenous oxygen difference (AVDO2), cerebral metabolic rate of oxygen (CMRO2), ventricular cerebrospinal fluid (CSF) lactate, and ICP values were obtained 1 hour before and 1 hour and 6 hours after a session in an HBO chamber. Patients were assigned to one of three categories according to whether they had reduced, normal, or raised CBF before HBO. In patients in whom CBF levels were reduced before HBO sessions, both CBF and CMRO2 levels were raised 1 hour and 6 hours after HBO (p < 0.05). In patients in whom CBF levels were normal before HBO sessions, both CBF and CMRO2 levels were increased at 1 hour (p < 0.05), but were decreased by 6 hours after HBO. Cerebral blood flow was reduced 1 hour and 6 hours after HBO (p < 0.05), but CMRO2 was unchanged in patients who had exhibited a raised CBF before an HBO session. In all patients AVDO2 remained constant both before and after HBO. Levels of CSF lactate were consistently decreased 1 hour and 6 hours after HBO, regardless of the patient's CBF category before undergoing HBO (p < 0.05). Intracranial pressure values higher than 15 mm Hg before HBO were decreased 1 hour and 6 hours after HBO (p < 0.05). The effects of each HBO treatment did not last until the next session in the hyperbaric chamber. CONCLUSIONS: The increased CMRO2 and decreased CSF lactate levels after treatment indicate that HBO may improve aerobic metabolism in severely brain injured patients. This is the first study to demonstrate a prolonged effect of HBO treatment on CBF and cerebral metabolism. On the basis of their data the authors assert that shorter, more frequent exposure to HBO may optimize treatment.     

Effects of hyperbaric oxygenation therapy on cerebral metabolism and intracranial pressure in severely brain injured patients

OBJECT: Hyperbaric oxygenation (HBO) therapy has been shown to reduce mortality by 50% in a prospective randomized trial of severely brain injured patients conducted at the authors' institution. The purpose of the present study was to determine the effects of HBO on cerebral blood flow (CBF), cerebral metabolism, and intracranial pressure (ICP), and to determine the optimal HBO treatment paradigm. METHODS: Oxygen (100% O2, 1.5 atm absolute) was delivered to 37 patients in a hyperbaric chamber for 60 minutes every 24 hours (maximum of seven treatments/patient). Cerebral blood flow, arteriovenous oxygen difference (AVDO2), cerebral metabolic rate of oxygen (CMRO2), ventricular cerebrospinal fluid (CSF) lactate, and ICP values were obtained 1 hour before and 1 hour and 6 hours after a session in an HBO chamber. Patients were assigned to one of three categories according to whether they had reduced, normal, or raised CBF before HBO. In patients in whom CBF levels were reduced before HBO sessions, both CBF and CMRO2 levels were raised 1 hour and 6 hours after HBO (p < 0.05). In patients in whom CBF levels were normal before HBO sessions, both CBF and CMRO2 levels were increased at 1 hour (p < 0.05), but were decreased by 6 hours after HBO. Cerebral blood flow was reduced 1 hour and 6 hours after HBO (p < 0.05), but CMRO2 was unchanged in patients who had exhibited a raised CBF before an HBO session. In all patients AVDO2 remained constant both before and after HBO. Levels of CSF lactate were consistently decreased 1 hour and 6 hours after HBO, regardless of the patient's CBF category before undergoing HBO (p < 0.05). Intracranial pressure values higher than 15 mm Hg before HBO were decreased 1 hour and 6 hours after HBO (p < 0.05). The effects of each HBO treatment did not last until the next session in the hyperbaric chamber. CONCLUSIONS: The increased CMRO2 and decreased CSF lactate levels after treatment indicate that HBO may improve aerobic metabolism in severely brain injured patients. This is the first study to demonstrate a prolonged effect of HBO treatment on CBF and cerebral metabolism. On the basis of their data the authors assert that shorter, more frequent exposure to HBO may optimize treatment.     

Aggravation of infarct formation by brain swelling in a large territorial stroke: a target for neuroprotection?

OBJECT: In territorial stroke vasogenic edema formation leads to elevated intracranial pressure (ICP) and can cause herniation and death. Brain swelling further impairs collateral blood flow to the ischemic penumbra and causes mechanical damage to adjacent brain structures. In the present study the authors sought to quantify the impact of this space-occupying effect on ischemic lesion formation. METHODS: Wistar rats were assigned to undergo bilateral craniectomy or a sham operation and then were subjected to temporary middle cerebral artery occlusion (MCAO) for 90 minutes. A clinical evaluation and 7-T MR imaging studies were performed 5 and 24 hours after MCAO. The absolute brain water content was determined at 24 hours by using the wet/dry method. RESULTS: Bilateral craniectomy before MCAO led to a drastic reduction in lesion volume at both imaging time points (p < 0.0001). Ischemic lesion volume was 2.7- and 2.3-fold larger in sham-operated animals after 5 and 24 hours, respectively. Clinical scores were likewise better in rats that had undergone craniectomy (p < 0.05). After 24 hours the midline shift differed significantly between the 2 groups (p < 0.001), but not after 5 hours. The relation between brain water content and ischemic lesion volume as well as the T2 relaxation time within the infarcted area was not different between the groups (p > 0.05). CONCLUSIONS: The data indicated that collateral damage caused by the space-occupying effect of a large MCA territory stroke contributes seriously to ischemic lesion formation. The elimination of increased ICP thus must be regarded as a highly neuroprotective measure, rather than only a life-saving procedure to prevent cerebral herniation. Further clinical trials should reveal the neuroprotective potential of surgical and pharmacological ICP-lowering therapeutic approaches.     

Superoxide dismutase does not prevent delayed hypoperfusion after incomplete cerebral ischaemia in the rat

Summary Local cerebral blood flow (1CBF) was measured autoradiographically 60 minutes after 15 minutes of forebrain ischaemia in rats treated with superoxide dismutase (SOD) before (50 mg · kg^–1 body weight) or at the end of the ischaemia period (4mg·kg^–1 body weight). Incomplete forebrain ischaemia was produced by a combination of common carotid artery occlusion and bleeding to a mean arterial blood pressure of 50 mmHg. During ischaemia the 1CBF values in cortical areas were less than 3% of the preischaemic values and treatment with SOD prior to ischaemia did not influence 1CBF during ischaemia. Sixty minutes after termination of cerebral ischaemia the 1CBF values were decreased to between 40 and 60% of values found in control animals. Neither form of treatment improved the postischaemic cerebral blood flows. The results imply that postischaemic flow disturbances in the brain may not be due to extracellular superoxide production.     

抗坏血酸对糖尿病大鼠肾脏缺血-再灌注后肾小球内皮多糖-蛋白复合物的影响

目的观察抗坏血酸预处理对糖尿病大鼠肾脏缺血-再灌注后肾小球内皮多糖-蛋白复合物的影响。方法 32只SD健康清洁大鼠随机均分为四组:A组为正常血糖大鼠,B、C、D组首先建立糖尿病模型,A、B组为假手术组,麻醉后行腹部正中切口,小心分离暴露双侧肾蒂游离肾动脉,30min后关闭腹腔;C组每天腹腔注射生理盐水0.5ml,15d后建立肾脏缺血-再灌注模型;D组每天腹腔注射抗坏血酸200 mg/kg 0.5 ml,15d后建立肾脏缺血-再灌注模型。观察大鼠术前30 min(T_1)、游离肾动脉后(T_2)、术后30 min(T_3)、术后6h(T_4)、术后24h(T_5)的血糖(Glu)、尿素氮(BUN)、肌酐(Cr)、丙二醛(MDA)、超氧化物歧化酶(SOD)的变化,检测术后24h半胱天冬酶-3(caspase-3)、细胞色素C(CytC)和多糖-蛋白复合物的表达情况。结果C、D组大鼠在T_3~T_5时BUN、Cr、MDA水平明显高于A、B组,SOD水平明显低于A、B组(P0.05)。与C组比较,D组大鼠T_3~T_5时BUN、Cr、MDA水平明显降低,SOD水平明显升高,caspase-3、CytC表达水平明显降低,肾小球内皮多糖-蛋白复合物的厚度明显增加,肾组织损伤明显改善(P0.05)。结论抗坏血酸预处理可通过减轻糖尿病大鼠肾缺血-再灌注后肾小球内皮多糖-蛋白复合物的损伤从而减轻糖尿病大鼠肾缺血-再灌注损伤。     

Whole-Brain Blood Flow and Oxygen Metabolism in the Rat After Halothane Anesthesia

A recent modification of the Kety-Schmidt wash-out technique for 133xenon was used to measure whole-brain blood flow (CBF) and oxygen consumption (CMRO2) 1 to 4 hours after termination of halothane anesthesia in 15 Wistar rats. In this 3-hour experimental period, mean CBF and CMRO2 were reduced to 29 and 43% of control values, respectively. CBF and CMRO2 determined at the beginning and end of the experimental period were not significantly different from each other. Cerebral venous O2 tension was significantly higher than in the control group, supporting recent suggestions of a primary, intrinsic effect of halothane on the homeostatic control of this variable. It is concluded that halothane is not useful for cerebral metabolic studies in the rat.